Novel Approaches to the Treatment of Idiopathic Intracranial Hypertension.

PURPOSE OF REVIEW: Idiopathic intracranial hypertension (IIH) typically affects women of childbearing age, is associated with recent weight gain, and can result in debilitating headache as well as papilledema that can cause vision loss. There have been advances in the medical and surgical treatment of affected patients with IIH that can improve outcomes and tolerability of therapy. RECENT FINDINGS: Medical treatment with agents that lower intracranial pressure through pathways other than carbonic anhydrase inhibition are being developed, and medically-directed weight loss as well as bariatric surgery now may be considered as primary therapy. New surgical options including venous sinus stenting have shown efficacy even with cases of severe vision loss. Our treatment options for IIH patients are becoming more diverse, and individualized treatment decisions are now possible to address specific components of the patient's disease manifestations and to lead to IIH remission.

Randomized trial of bilateral gene therapy injection for m.11778G>A MT-ND4 Leber optic neuropathy.

Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G>A mutation in the MT-ND4 gene being the most common disease-causing mtDNA variant worldwide. The REFLECT phase 3 pivotal study is a randomized, double-masked, placebo-controlled trial investigating the efficacy and safety of bilateral intravitreal injection of lenadogene nolparvovec in patients with a confirmed m.11778G>A mutation, using a recombinant adeno-associated virus vector 2, serotype 2 (rAAV2/2-ND4). The first-affected eye received gene therapy; the fellow (affected/not-yet-affected) eye was randomly injected with gene therapy or placebo. The primary end point was the difference in change from baseline of best-corrected visual acuity (BCVA) in second-affected/not-yet-affected eyes treated with lenadogene nolparvovec versus placebo at 1.5 years post-treatment, expressed in logarithm of the minimal angle of resolution (LogMAR). Forty-eight patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in BCVA was not statistically different between second-affected/not-yet-affected eyes receiving lenadogene nolparvovec and placebo (primary end point). A statistically significant improvement in BCVA was reported from baseline to 1.5 years in lenadogene nolparvovec-treated eyes: -0.23 LogMAR for the first-affected eyes of bilaterally treated patients (P < 0.01); and -0.15 LogMAR for second-affected/not-yet-affected eyes of bilaterally treated patients and the first-affected eyes of unilaterally treated patients (P < 0.05). The mean improvement in BCVA from nadir to 1.5 years was -0.38 (0.052) LogMAR and -0.33 (0.052) LogMAR in first-affected and second-affected/not-yet-affected eyes treated with lenadogene nolparvovec, respectively (bilateral treatment group). A mean improvement of -0.33 (0.051) LogMAR and -0.26 (0.051) LogMAR was observed in first-affected lenadogene nolparvovec-treated eyes and second-affected/not-yet-affected placebo-treated eyes, respectively (unilateral treatment group). The proportion of patients with one or both eyes on-chart at 1.5 years was 85.4% and 72.0% for bilaterally and unilaterally treated patients, respectively. The gene therapy was well tolerated, with no systemic issues. Intraocular inflammation, which was mostly mild and well controlled with topical corticosteroids, occurred in 70.7% of lenadogene nolparvovec-treated eyes versus 10.2% of placebo-treated eyes. Among eyes treated with lenadogene nolparvovec, there was no difference in the incidence of intraocular inflammation between bilaterally and unilaterally treated patients. Overall, the REFLECT trial demonstrated an improvement of BCVA in LHON eyes carrying the m.11778G>A mtDNA mutation treated with lenadogene nolparvovec or placebo to a degree not reported in natural history studies and supports an improved benefit/risk profile for bilateral injections of lenadogene nolparvovec relative to unilateral injections.

Vessel Density Features of Optical Coherence Tomography Angiography for Classification of Optic Neuropathies Using Machine Learning.

BACKGROUND: To evaluate the classification performance of machine learning based on the 4 vessel density features of peripapillary optical coherence tomography angiography (OCT-A) for classifying healthy, nonarteritic anterior ischemic optic neuropathy (NAION), and optic neuritis (ON) eyes. METHODS: Forty-five eyes of 45 NAION patients, 32 eyes of 32 ON patients, and 76 eyes of 76 healthy individuals with optic nerve head OCT-A were included. Four vessel density features of OCT-A images were developed using a threshold-based segmentation method and were integrated in 3 models of machine learning classifiers. Classification performances of support vector machine (SVM), random forest, and Gaussian Naive Bayes (GNB) models were evaluated with the area under the receiver-operating-characteristic curve (AUC) and accuracy. RESULTS: We divided 121 images into a 70% training set and 30% test set. For ON-NAION classification, best results were achieved with 50% threshold, in which 3 classifiers (SVM, RF, and GNB) discriminated ON from NAION with an AUC of 1 and accuracy of 1. For ON-Normal classification, with 100% threshold, SVM and RF classifiers were able to discriminate normal from ON with AUCs of 1 and accuracies of 1. For NAION-normal classification, with 50% threshold, the SVM and RF classified the NAION from normal with AUC and accuracy of 1. CONCLUSIONS: ML based on the combined peripapillary vessel density features of total vessels and capillaries in the whole image and ring image could provide excellent performance for NAION and ON distinction.

Insights into spaceflight-associated neuro-ocular syndrome with review of intraocular and orbital findings.

PURPOSE OF REVIEW: Spaceflight-associated neuro-ocular syndrome (SANS) remains a phenomenological term, and advances in ophthalmic imaging as well as new insights from ground-based experiments have given support to new theories of how SANS develops and what may be done to counter it. RECENT FINDINGS: SANS has been postulated to arise from elevated intracranial pressure (ICP) during long-duration spaceflight (LDSF). However, recent work has shown that acute microgravity exposure does not increase ICP, and the effect of cephalad fluid shifts on ICP in microgravity remain unknown. In addition, structural imaging of the retina and optic nerve show changes after LDSF that are distinct from findings in terrestrial patients with elevated ICP. Since astronauts have not reported symptoms that would be expected with chronic ICP elevation, new theories that orbital and/or intracranial venous pressure may be the primary contributors to the development of SANS. SUMMARY: Research has been filling knowledge gaps that exist regarding the cause(s) of SANS, and these advances are crucial steps in the effort to design countermeasures that will be required before human deep space exploration missions can be undertaken.

Efficacy of teprotumumab therapy in patients with long-duration thyroid eye disease.

PURPOSE OF REVIEW: Teprotumumab, an inhibitor of the insulin-like growth factor 1 receptor (IGF-1R), was approved by the US Food and Drug Administration in January 2020 for the treatment of thyroid eye disease (TED). The clinical trials leading to its approval enrolled patients with recent disease onset and significant inflammatory symptoms and signs. Subsequent real-world teprotumumab use in patients with longer duration of disease also may be effective, and there have been several publications reporting on experience in these patient groups. RECENT FINDINGS: TED results in disfiguring changes such as ocular proptosis and affects visual function by altering extraocular muscle function, leading to diplopia. Compressive optic neuropathy also may occur, and disease manifestations may persist for years. Teprotumumab treatment in cases of TED in which prior interventions (medical or surgical) had failed, or in treatment-naïve patients whose disease had been stable for years, has been reported to improve both clinical signs and symptoms (proptosis, diplopia) and to reduce the pathologic orbital changes as assessed by orbital imaging. SUMMARY: Teprotumumab may be an appropriate treatment for TED regardless of disease duration and irrespective of the presence or absence of markers of active inflammation within the orbit.

Orbital Compartment Syndrome in Severe Burns: Predictive Factors, Timing, and Complications of Intervention.

PURPOSE: Severe burn patients require high-volume fluid resuscitation, which increases risk for orbital compartment syndrome (OCS). We aimed to understand surgeons' practice patterns and to examine risk factors for OCS, timing of lateral canthotomy and cantholysis (LCC), and complications of intervention. METHODS: A survey of American Society of Ophthalmic Plastic and Reconstructive Surgery and North American Society of Academic Orbital Surgeons' practice patterns in burn patients was undertaken. In addition, a retrospective analysis was conducted of 107 patients with burns greater than 20% total body surface area at 1 institution from January 1, 2009, to June 1, 2018. Patients with Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis, frostbite, or no ophthalmologic consultation were excluded. Risk factors for OCS, timing of LCC, and complications of the intervention were examined. RESULTS: In the survey, 37 of 54 respondents had treated burn patients, of which 29 followed no protocol. Threshold intraocular pressure for intervention varied widely, and nearly all reported having seen complications from LCC in burn patients. For the retrospective analysis, 107 patients met criteria, of which 22 (20.6%) required LCC. Renal failure, inhalation injury, eyelid burns, higher total body surface area, elevated lactate, increased number of escharotomies, and greater total fluid required were significantly associated with the clinical decision that the patient was at risk for OCS requiring LCC. Fluid resuscitation in excess of the Ivy Index (250 ml/kg) increased odds of LCC 8.6 times. Average time of LCC was 15.8 hours after burn. LCC patients experienced higher rates of complications including eyelid retraction, exposure keratopathy, and corneal ulceration. CONCLUSIONS: Severe burn patients should be monitored closely by an ophthalmologist during the first 48 hours for signs of OCS. Further studies should aim to recommend protocols guiding evaluation and intervention.

Ophthalmic Trauma Correlation Matrix (OTCM): a potential novel tool for evaluation of concomitant ocular tissue damage in open globe injuries.

PURPOSE: To introduce a novel tool to investigate the correlation between concomitant injuries and primary open globe injury (OGI) in the setting of ophthalmic trauma, the "Ophthalmic Trauma Correlation Matrix" (OTCM). METHODS: Retrospective cohort review, performed at a tertiary referral eye care center in Eastern Nepal, involving all eyes with OGI meeting the inclusion criteria from 2015-2018. Clinical data including details of primary injury, concurrent injuries, and clinical course were noted from hospital medical records. A correlation matrix chart was devised using matrix correlation and Pearson's correlation coefficient. This chart was then used to evaluate the association of the various injuries in the setting of OGI. RESULTS: A total of 109 eyes with OGI were included. Majority of the eyes (78, 71.6%) had zone I injuries, while most of the eyes (66, 60.6%) had penetrating injury. The most frequent concomitant injuries in all zones of OGI were traumatic lens injury (77, 70.64%), followed by hyphema (48, 44.03%), and vitreous hemorrhage (35, 32.11%). The most common concomitant injury associated with zone I was hyphema (0.873), while traumatic subluxation/cataract (0.894) and vitreous hemorrhage (0.972) were commonly associated with zone II and III, respectively. CONCLUSIONS: OTCM could be a useful tool to manage injuries related to the primary ocular injury. This additional information will aid in the prognostication, planning, and management of OGI and potentially prevent repeat surgeries and inadequate treatments.

The application of clinical registries in ophthalmic trauma-the International Globe and Adnexal Trauma Epidemiology Study (IGATES).

Ophthalmic trauma is a leading cause of preventable monocular blindness worldwide. The prevalence of ophthalmic trauma varies considerably based on geographic location, socio-economic status, age groups, occupation, and cultural practices such as firework celebrations. Clinical registries are known to be valuable in guiding the diagnosis, management, and prognostication of complex diseases. However, there is currently a lack of a centralized international data repository for ophthalmic trauma. We draw lessons from past and existing clinical registries related to ophthalmology and propose a new suitable international multicenter clinical registry for ophthalmic trauma: the International Globe and Adnexal Trauma Epidemiology Study (IGATES). IGATES is hosted on a secure web-based platform which exhibits user-friendly smart features, an integrated Ocular Trauma Score (OTS) prognosis calculator, efficient data collection points, and schematic graphical software. IGATES currently has 37 participating centers globally. The data collected through IGATES will be primarily used to develop a more robust and improved ophthalmic trauma prognostic classification system, the Ocular Trauma Score-2 (OTS-2), which builds on previous systems such as the Birmingham Eye Trauma Terminology System (BETTS) and Ocular Trauma Score (OTS). Furthermore, IGATES will act as a springboard for further research into the epidemiology, diagnosis, and management of ophthalmic trauma. Ultimately, IGATES serves to advance the field of ophthalmic trauma and improve the care that patients with ophthalmic trauma receive.

Mismatch in Supply and Demand for Neuro-Ophthalmic Care.

BACKGROUND: Previous research suggests the number of neuro-ophthalmologists in the United States may be below a level that provides sufficient access to neuro-ophthalmic care in much of the United States. However, national estimates of the amount of clinical time spent on neuro-ophthalmology are lacking. METHODS: The North American Neuro-Ophthalmology Society administered a survey on professional time allocation to its active members. Survey response was 95%. The survey characterized the hours each week each respondent allocated to overall work, clinical work, clinical work in ophthalmology/neurology, and clinical work in neuro-ophthalmology specifically. The survey additionally collected information regarding demographics, current wait times to be seen for new patients, and the difference in clinical time spent in neuro-ophthalmology spent between the current day compared with that shortly after completing clinical training. Linear regression was used to identify potential relationships between the above and average wait time. RESULTS: On average, responding physicians spent 70% of their clinical time on neuro-ophthalmology. In 6 states, there were no reported practicing neuro-ophthalmologists, and in only 8 states was the clinical full-time equivalent to population ratio below the suggested threshold of 1 for every 1.2 million. The median wait time for a new patient was 6 weeks. This wait time was associated with the fraction of clinical time spent in neuro-ophthalmology (0.2 weeks longer wait for a 10 percentage point increase in the fraction of time spent in neuro-ophthalmology; P = 0.02), and suggestively associated with training (training in ophthalmology was associated with 1.0 week shorter wait time; P = 0.06). CONCLUSION: The survey suggests that neuro-ophthalmologists are unable to see patients in a timely manner and a decreasing number of clinicians are entering the field. Future interventions should be considered to incentivize neuro-ophthalmology training in ophthalmology and neurology residents such that the United States population is able to appropriately access neuro-ophthalmic care.

An Exploratory Study to Investigate the Utility of Clinical Screening for Neurodegenerative Disease in Age-Related Eye Disease Research.

BACKGROUND: Unrecognized neurodegenerative diseases (NDD) in age-related eye disease research studies have the potential to confound vision-specific quality of life and retinal optical coherence tomography (OCT) outcome measures. The aim of this exploratory study was to investigate relationships between NDD screening tools and visual outcome measures in a small cohort of controls from the Colorado Age-Related Macular Degeneration Registry (CO-AMD), to consider the utility of future studies. METHODS: Twenty-nine controls from the CO-AMD were screened using the Montreal Cognitive Assessment (MoCA), a Colorado Parkinsonian Checklist, and the Lewy Body Composite Risk Score. Univariate and multivariable linear regression modeling was used to assess associations between screening tools and the National Eye Institute Visual Function Questionnaire-25 (VFQ-25) and macular OCT outcome measures, and t tests were used to evaluate outcome measure differences between those with normal vs abnormal MoCA scores. RESULTS: One patient withdrew. The average age was 72.8 years, and 68% were female patients. Ten participants (36%) had abnormal MoCA scores, and their VFQ-25 scores were only 1 point less and not statistically different than those with normal MoCA scores. Macular OCT volumes and thicknesses for retinal nerve fiber layer (RNFL) and retinal ganglion cell layer were consistently and moderately lower for those with abnormal MoCA scores, and a positive association between MoCA and macular RNFL volume was observed, although differences and regression were not significant. Parkinson screening tests were abnormal for only 4 participants and were not associated with OCT or VFQ-25 measures by regression modeling. CONCLUSIONS: Given the degree and direction of observed differences, further investigation is warranted regarding the relationship between cognitive screening tools and macular OCT measures in age-related eye disease research, but future investigations regarding the relationship between NDD screening tools and VFQ-25 seem unwarranted.

Cavernous Malformation of the Optic Nerve and Chiasm: Prompt Suspicion and Surgery Matter.

BACKGROUND: Cavernous malformations (CMs) of the optic nerve and chiasm are extremely rare, accounting for less than 1% of all intracranial CMs. Acute, subacute, or progressive visual loss from CM may occur with or without hemorrhage. Prompt surgical excision of the CM offers the best hope to improve or stabilize vision. Given its rarity, optic nerve and chiasm CMs may not be readily suspected. We provide 3 cases of optic nerve and chiasm CM, highlighting key neuroimaging features and the importance of expedited intervention. METHODS: Case records of the neuro-ophthalmology clinics of the Bascom Palmer Eye Institute and the University of Colorado, and literature review of reported cases of optic CM. RESULTS: A 49-year-old woman reported acute progressive painless vision loss in the right eye. MRI showed a suprasellar mass with heterogeneity in signal involving the right prechiasmatic optic nerve. Surgical excision of the CM 5 days after onset of visual loss improved vision from 20/300 to 20/30. A 29-year-old woman with acute painless blurred vision in the right eye had anterior chiasmal junctional visual field defects corresponding to a heterogeneously minimally enhancing mass with blood products enlarging the optic chiasm and proximal right optic nerve. Surgical excision of the CM 8 weeks after onset of visual loss improved vision from 20/40 to 20/15 with improved visual fields. A 33-year-old woman with a history of familial multiple CMs, diagnosed at age 18, reported new-onset severe headache followed by blurred vision. MRI showed a hemorrhagic lesion of the optic chiasm and right optic tract. She was 20/20 in each eye with a reported left superior homonymous hemianopia. No intervention was recommended. Vision of the right eye worsened to 20/400 2 months later. The patient was followed over 13 years, and the MRI and visual function remained unchanged. Literature review yielded 87 optic CM cases occurring across gender and nearly all ages with visual loss and headache as the most common presenting symptoms. Optic chiasm is the most common site of involvement (79%). Nearly 95% of reported CM cases were treated with surgery with 81% with improved vision and 1% with worsened vision. CONCLUSION: MRI features are critical to the diagnosis of optic nerve and chiasm CM and may mimic other lesions. A high index of suspicion by the neuro-ophthalmologist and neuroradiologist leads to early recognition and intervention. Given optic CM displaces and does not infiltrate neural tissue, expedited surgical resection by a neurosurgeon after consideration of other diagnostic possibilities improves visual function in most cases.

A Lesson Learnt from a Dural Carotid Cavernous Fistula-induced Superior Ophthalmic Vein Occlusion with Posterior Ischaemic Optic Neuropathy.

We report a 64-year-old male patient without any contributory medical history who visited the eye clinic due to right-sided headache for 1 month and then loss of vision for 3 days. The clinical presentation suggested a cavernous sinus syndrome and acute optic nerve ischaemia in his right eye. The left eye was normal. Orbit and brain magnetic resonance (MR) imaging demonstrated restricted diffusion of the posterior orbital segment of the right optic nerve, suggesting an acute posterior ischaemic optic neuropathy. Three-dimensional time-of-flight MR angiography showed high flow in the right cavernous sinus, indicating a carotid cavernous fistula (CCF). In the arterial phase of digital subtraction angiography (DSA), a fistula in the right cavernous sinus was revealed which was fed by meningeal branches from both the external and internal carotid arteries, confirming an indirect CCF. The origin of the right ophthalmic artery was seen, but its branches were not detected. Right common carotid artery DSA showed a superior ophthalmic vein occlusion and the drainage vein of the CCF ran through the inferior petrosal sinus to the internal jugular vein. The right cavernous sinus was embolised using platinum coils and glue to occlude the feeding vessels from the branches of both the external and internal carotid arteries. Post-embolisation imaging showed complete closure of the fistula.

Follow-up of Nonarteritic Anterior Ischemic Optic Neuropathy With Optical Coherence Tomography Angiography.

BACKGROUND: Peripapillary and macular microvasculature alterations after nonarteritic ischemic optic neuropathy (NAION) have been investigated in several studies. We aimed to explore the vascular changes from acute NAION (aNAION) to chronic NAION (cNAION). METHODS: This prospective observational study composed of 16 eyes with aNAION and 40 healthy age-matched controls. Eyes with NAION were followed up for more than 6 months after acute event. Optical coherence tomography angiography (OCTA) was used to evaluate peripapillary and macular vessel densities (VDs). The customized software was used for calculating deep retinal VD to attenuate the large superficial vessel projection effect. RESULT: The mean age of patients with NAION and controls was 56.13 ± 13.2 and 54.46 ± 15.5 years, respectively (P = 0.195). Radial peripapillary capillary density was significantly lower in both eyes with aNAION and eyes with cNAION than healthy eyes. Peripapillary capillary density decreased significantly from the acute to the chronic phase of NAION with values of 41.77 ± 4.05% and 34.35 ± 7.30%, respectively (P < 0.001). The mean superficial macular VD was 46.83 ± 3.47% in aNAION and 44.49 ± 4.50% in cNAION eyes with no significant difference between them (P = 0.252), but both were lower than control eyes. Deep macular VD was not affected in aNAION and cNAION eyes compared with control eyes. Correlation analysis in eyes with cNAION revealed that there were significant correlations between peripapillary nerve fiber layer and the capillary density (r = 0.772, P < 0.001) and between ganglion cell complex thickness and corresponding superficial macular VD. CONCLUSIONS: Although a decrease in peripapillary capillary density in aNAION eyes with active disc edema progressed when evaluated in the cNAION state, progressive VD loss was not observed in the macular area, suggesting a nonprogressive nature of macular vessel involvement in NAION.

Acute Complete Oculomotor Nerve Palsy in a Young Male Due to a Skull Base Myofibroma.

ABSTRACT: A 25-year-old male patient visited the ophthalmology clinic because of upper eye lid ptosis in the right eye, binocular double vision, and light sensitivity. He was diagnosed with a complete third nerve palsy caused by a skull base myofibroma, a rare clinical entity that has not been described before in oculomotor nerve palsy.

Detection of Optic Disc Abnormalities in Color Fundus Photographs Using Deep Learning.

BACKGROUND: To date, deep learning-based detection of optic disc abnormalities in color fundus photographs has mostly been limited to the field of glaucoma. However, many life-threatening systemic and neurological conditions can manifest as optic disc abnormalities. In this study, we aimed to extend the application of deep learning (DL) in optic disc analyses to detect a spectrum of nonglaucomatous optic neuropathies. METHODS: Using transfer learning, we trained a ResNet-152 deep convolutional neural network (DCNN) to distinguish between normal and abnormal optic discs in color fundus photographs (CFPs). Our training data set included 944 deidentified CFPs (abnormal 364; normal 580). Our testing data set included 151 deidentified CFPs (abnormal 71; normal 80). Both the training and testing data sets contained a wide range of optic disc abnormalities, including but not limited to ischemic optic neuropathy, atrophy, compressive optic neuropathy, hereditary optic neuropathy, hypoplasia, papilledema, and toxic optic neuropathy. The standard measures of performance (sensitivity, specificity, and area under the curve of the receiver operating characteristic curve (AUC-ROC)) were used for evaluation. RESULTS: During the 10-fold cross-validation test, our DCNN for distinguishing between normal and abnormal optic discs achieved the following mean performance: AUC-ROC 0.99 (95 CI: 0.98-0.99), sensitivity 94% (95 CI: 91%-97%), and specificity 96% (95 CI: 93%-99%). When evaluated against the external testing data set, our model achieved the following mean performance: AUC-ROC 0.87, sensitivity 90%, and specificity 69%. CONCLUSION: In summary, we have developed a deep learning algorithm that is capable of detecting a spectrum of optic disc abnormalities in color fundus photographs, with a focus on neuro-ophthalmological etiologies. As the next step, we plan to validate our algorithm prospectively as a focused screening tool in the emergency department, which if successful could be beneficial because current practice pattern and training predict a shortage of neuro-ophthalmologists and ophthalmologists in general in the near future.

Neuro-Ophthalmic Complications in Patients Treated With CTLA-4 and PD-1/PD-L1 Checkpoint Blockade.

BACKGROUND: In recent years, CTLA-4 and PD-1/PD-L1 checkpoint inhibitors have proven to be effective and have become increasingly popular treatment options for metastatic melanoma and other cancers. These agents work by enhancing autologous antitumor immune responses. Immune-related ophthalmologic complications have been reported in association with checkpoint inhibitor use but remain incompletely characterized. This study seeks to investigate and further characterize the neuro-ophthalmic and ocular complications of immune checkpoint blockade treatment. METHODS: A survey was distributed through the secure electronic data collection tool REDCap to neuro-ophthalmology specialists in the North American Neuro-Ophthalmology Society listserv. The study received human subjects approval through the University of California at Los Angeles Institutional Review Board. The survey identified patients sent for neuro-ophthalmic consultation while receiving one or more of a PD-1 inhibitor (pembrolizumab, nivolumab, or cemiplimab); PD-L1 inhibitor (atezolizumab, avelumab, or durvalumab); or the CTLA-4 inhibitor ipilimumab. Thirty-one patients from 14 institutions were identified. Patient demographics, neuro-ophthalmic diagnosis, diagnostic testing, severity, treatment, clinical response, checkpoint inhibitor drug used, and cancer diagnosis was obtained. RESULTS: The checkpoint inhibitors used in these patients included pembrolizumab (12/31), nivolumab (6/31), combined ipilimumab with nivolumab (7/31, one of whom also received pembrolizumab during their course of treatment), durvalumab (3/31), ipilimumab (2/31), and cemiplimab (1/31). Malignant melanoma (16/31) or nonsmall cell lung carcinoma (6/31) were the most common malignancies. The median time between first drug administration and the time of ophthalmological symptom onset was 14.5 weeks. Eleven patients had involvement of the optic nerve, 7 patients had inflammatory orbital or extraocular muscle involvement, 6 patients had ocular involvement from neuromuscular junction dysfunction, 4 patients had cranial nerve palsy, and 4 patients had non neuro-ophthalmic complications. Use of systemic corticosteroids with or without stopping the checkpoint inhibitor resulted in improvement of most patients with optic neuropathy, and variable improvement for the other ophthalmic conditions. CONCLUSION: This study describes the variable neuro-ophthalmic adverse events associated with use of immune checkpoint inhibitors and contributes a more thorough understanding of their clinical presentations and treatment outcomes. We expect this will increase awareness of these drug complications and guide specialists in the care of these patients.

Persistent Globe Flattening in Astronauts following Long-Duration Spaceflight.

Posterior globe flattening has been well-documented in astronauts both during and after long-duration space flight (LDSF) and has been observed as early as 10 days into a mission on the International Space Station. Globe flattening (GF) is thought to be caused by the disc centred anterior forces created by elevated volume and/or pressure within the optic nerve sheath (ONS). This might be the result of increased intracranial pressure, increased intraorbital ONS pressure from compartmentalisation or a combination of these mechanisms. We report posterior GF in three astronauts that has persisted for 7 years or more following their return from LDSFs suggesting that permanent scleral remodelling may have occurred.

Visual hallucinations in psychiatric, neurologic, and ophthalmologic disease.

PURPOSE OF REVIEW: Recent studies have increased our understanding of the biochemical and structural bases of visual hallucinations in patients with a variety of underlying causes. RECENT FINDINGS: Visual hallucinations may be related to disruption of functional connectivity networks, with underlying biochemical dysfunction such as decreased in cholinergic activity. Structural abnormalities in primary and higher order visual processing areas also have been found in patients with visual hallucinations. The occurrence of visual hallucinations after vision loss, the Charles Bonnet syndrome, may have more functional similarity to psychiatric and neurodegenerative causes than previously suspected despite retained insight into the unreal nature of the phenomena. SUMMARY: Visual hallucinations are common, and patients may not report them if specific inquiries are not made. Presence or absence of hallucinations may be of diagnostic and therapeutic importance, especially in patients with neurodegenerative conditions that have overlapping features. Treatment of visual hallucinations remains challenging and must be tailored to each patient based on the underlying cause and comorbid conditions.

Considerations for the Treatment of Inflammatory Neuro-Ophthalmologic Disorders During the COVID-19 Pandemic.

The initiation and continuation of immune-based therapies to treat and prevent complications of inflammatory neuro-ophthalmologic disorders during the 2019 novel coronavirus (COVID-19) pandemic is the subject of considerable debate. In each case, a treatment decision must be reached based on best clinical practices for the disorder, patient comorbidities, the current state of knowledge about the pathogenesis and infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the utilization of hospital and community resources. Unfortunately, the evidence needed to standardize the decision-making process for each neuro-ophthalmologic disorder is currently absent and is likely to require months or years to develop based on the accrual of robust international data sets. In this article, we review the current understanding of SARS-CoV-2 and COVID-19 complications to provide a framework for approaching the treatment of inflammatory neuro-ophthalmic disorders during the COVID-19 viral pandemic.

Deep Learning and Transfer Learning for Optic Disc Laterality Detection: Implications for Machine Learning in Neuro-Ophthalmology.

BACKGROUND: Deep learning (DL) has demonstrated human expert levels of performance for medical image classification in a wide array of medical fields, including ophthalmology. In this article, we present the results of our DL system designed to determine optic disc laterality, right eye vs left eye, in the presence of both normal and abnormal optic discs. METHODS: Using transfer learning, we modified the ResNet-152 deep convolutional neural network (DCNN), pretrained on ImageNet, to determine the optic disc laterality. After a 5-fold cross-validation, we generated receiver operating characteristic curves and corresponding area under the curve (AUC) values to evaluate performance. The data set consisted of 576 color fundus photographs (51% right and 49% left). Both 30° photographs centered on the optic disc (63%) and photographs with varying degree of optic disc centration and/or wider field of view (37%) were included. Both normal (27%) and abnormal (73%) optic discs were included. Various neuro-ophthalmological diseases were represented, such as, but not limited to, atrophy, anterior ischemic optic neuropathy, hypoplasia, and papilledema. RESULTS: Using 5-fold cross-validation (70% training; 10% validation; 20% testing), our DCNN for classifying right vs left optic disc achieved an average AUC of 0.999 (±0.002) with optimal threshold values, yielding an average accuracy of 98.78% (±1.52%), sensitivity of 98.60% (±1.72%), and specificity of 98.97% (±1.38%). When tested against a separate data set for external validation, our 5-fold cross-validation model achieved the following average performance: AUC 0.996 (±0.005), accuracy 97.2% (±2.0%), sensitivity 96.4% (±4.3%), and specificity 98.0% (±2.2%). CONCLUSIONS: Small data sets can be used to develop high-performing DL systems for semantic labeling of neuro-ophthalmology images, specifically in distinguishing between right and left optic discs, even in the presence of neuro-ophthalmological pathologies. Although this may seem like an elementary task, this study demonstrates the power of transfer learning and provides an example of a DCNN that can help curate large medical image databases for machine-learning purposes and facilitate ophthalmologist workflow by automatically labeling images according to laterality.